An Open-Label, Multi-Centre, Single-Arm, Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Efficacy of IMM2510 in Combination With IMM27M in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- IMM27M
- Conditions
- Advanced Solid Tumors
- Sponsor
- ImmuneOnco Biopharmaceuticals (Shanghai) Inc.
- Enrollment
- 108
- Locations
- 1
- Primary Endpoint
- DLT/MTD (Dose Escalation Phase)
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This study is an open-label, multi-centre, single-arm, phase I clinical study, to evaluate the safety, tolerability, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of IMM2510 (an anti-PD-L1/VEGF bispecific antibody fusion protein) + IMM27M (a humanized Fc-engineered anti-CTLA-4 antibody) combination therapy in patients with advanced solid tumors.
Detailed Description
Dose Escalation Phase: 3+3 Dose escalation design of IMM27M + IMM2510 combination therapy in advanced solid tumors. Dose Expansion Phase: Recommended dose for expansion (RDE) of IMM27M + IMM2510 combination therapy in three cohorts: cohort 1: locally advanced unresectable or metastatic triple-negative breast cancer (those with at least first-line systemic treatment failure or intolerance); cohort 2: advanced hepatocellular carcinoma (patients with at least first-line systemic therapy failure or intolerance); cohort 3: other advanced solid tumors (those with at least first-line systemic treatment failure or intolerance).
Investigators
Eligibility Criteria
Inclusion Criteria
- •The patient can understand the procedures and methods of this clinical trial. After giving full informed consent, the patient voluntarily participates in it and signs the informed consent form.
- •Aged between 18 and 75 years old (including both ends), regardless of gender.
- •Clinical diagnosis:
- •Dose escalation phase: Patients with advanced malignant solid tumors confirmed by histology or cytology, who have failed previous standard treatments, have no standard treatment regimens or are not suitable for standard treatment at present, including but not limited to hepatocellular carcinoma, triple-negative breast cancer, soft tissue sarcoma, non-small cell lung cancer, epithelial ovarian cancer, small cell lung cancer, malignant melanoma, colorectal cancer, ovarian cancer, endometrial cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck, etc.
- •Dose expansion phase: The following tumor types are included: a. Patients with advanced hepatocellular carcinoma who have failed or could not tolerate at least one line of previous systemic treatment; b. Patients with locally advanced, unresectable or metastatic triple-negative breast cancer confirmed by histology or cytology, who have failed or could not tolerate at least one line of previous systemic treatment; c. Patients with other advanced malignant solid tumors (except those with triple-negative breast cancer and advanced hepatocellular carcinoma) confirmed by histology or cytology, who have failed or could not tolerate at least one line of previous systemic treatment, including but not limited to soft tissue sarcoma, non-small cell lung cancer, epithelial ovarian cancer, small cell lung cancer, malignant melanoma, colorectal cancer, ovarian cancer, endometrial cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck, etc.
- •Dose escalation phase: According to RECIST version 1.1, there should be at least one evaluable tumor lesion; Dose expansion phase: According to RECIST version 1.1, there should be at least one measurable tumor lesion.
- •ECOG performance status score of 0 -
- •The expected survival time is more than 3 months.
- •There should be sufficient organ function. Hematological system (without receiving blood transfusion or hematopoietic stimulating factor treatment within 14 days): Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, Platelet count (PLT) ≥ 100 × 10⁹/L, Hemoglobin (Hb) ≥ 90 g/L. For patients with HCC accompanied by liver cirrhosis, ANC ≥ 1.0 × 10⁹/L and platelet count ≥ 90 × 10⁹/L are acceptable for enrollment.
- •Liver function: Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN), for patients with liver metastasis or liver cancer, TBIL ≤ 3.0 × ULN; Alanine aminotransferase (ALT) ≤ 2.5 × ULN, for patients with liver metastasis or liver cancer, ALT ≤ 5.0 × ULN; Aspartate aminotransferase (AST) ≤ 2.5 × ULN, for patients with liver metastasis or liver cancer, AST ≤ 5.0 × ULN.
Exclusion Criteria
- •Patients meeting any one of the following criteria will be excluded from this study:
- •Previous treatment history:
- •Patients who received mitomycin and nitrosourea chemotherapy within 6 weeks before the first administration.
- •Patients who received the last systemic anti-tumor treatment, including chemotherapy, radiotherapy, immunotherapy, biological agents or endocrine therapy, etc., within 4 weeks before the first administration.
- •Patients who received hormonal anti-tumor treatment or small molecule targeted therapy within 2 weeks before the first administration.
- •Patients who received local treatment such as radiotherapy for target lesions within 4 weeks before the first administration, and those who received palliative local treatment for non-target lesions within 2 weeks before the first administration.
- •Patients who received non-specific immunomodulatory treatment (such as interleukin, interferon, thymosin, tumor necrosis factor, etc., excluding IL-11 used for treating thrombocytopenia) within 2 weeks before the first administration.
- •Patients who previously received the experimental drugs IMM2510 and/or IMM27M; those who could not tolerate treatment with anti-CTLA-4 or PD-1/L1 inhibitors (due to toxic and side effects); those who previously used drugs targeting three targets, namely anti-PD-1/L1, VEGF, and CTLA-4 simultaneously in the same regimen.
- •Patients who received traditional Chinese medicine with anti-tumor indications within 1 week before the first administration.
- •Patients who participated in other clinical trials within 4 weeks before the first administration.
Arms & Interventions
IMM2510 + IMM27M Combination Therapy
Dose Escalation Phase: Participants will receive IMM27M 3.0 mg/kg single dose on day 1 (C1D1), and after a 4-week interval, will receive IMM2510 10.0 mg/kg or 20.0 mg/kg dose every 2 weeks (Q2W). Dose Expansion Phase: The dose of IMM27M and IMM2510 for the dose expansion phase is determined according to the dose escalation results. Participants will receive IMM27M single dose on day 1 (C1D1), and after a 4-week interval, will receive IMM2510 every 2 weeks (Q2W).
Intervention: IMM27M
IMM2510 + IMM27M Combination Therapy
Dose Escalation Phase: Participants will receive IMM27M 3.0 mg/kg single dose on day 1 (C1D1), and after a 4-week interval, will receive IMM2510 10.0 mg/kg or 20.0 mg/kg dose every 2 weeks (Q2W). Dose Expansion Phase: The dose of IMM27M and IMM2510 for the dose expansion phase is determined according to the dose escalation results. Participants will receive IMM27M single dose on day 1 (C1D1), and after a 4-week interval, will receive IMM2510 every 2 weeks (Q2W).
Intervention: IMM2510
Outcomes
Primary Outcomes
DLT/MTD (Dose Escalation Phase)
Time Frame: Within 8 weeks after the investigational products administration (within 56 days after first dosing of C1D1)
Incidence and characteristics of Dose-Limiting Toxicity (DLT) to determine the Maximum Tolerated Dose (MTD).
RP2D (Dose Extension Phase)
Time Frame: From the first dose until disease progresses or end of treatment for other reasons, the maximum treatment duration is not more than 48 weeks
Recommended Phase II Dose (RP2D) of IMM27M and IMM2510, as the dose for efficacy study in Phase II, will be the dose with promising clinical responses observed in the patients, and well tolerated by patients.
Incidence and characteristics of AEs and SAEs (according to NCI CTCAE 5.0)
Time Frame: From the first dose to 30 days after the last dose [90 days for SAEs and Immune-related Adverse Event (irAEs) ], or until beginning new anti-tumor treatment
Incidence and characteristics of Adverse Events (AEs) and Serious Adverse Events (SAEs) throughout the study period, were evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) V5.0.
Secondary Outcomes
- ORR(From date of first dose until the date of first documented progression, death from any cause, loss of follow-up, withdrawal of informed consent, or study termination by the sponsor, whichever came first, assessed up to approximately 2 years)
- DCR(From date of first dose until the date of first documented progression, death from any cause, loss of follow-up, withdrawal of informed consent, or study termination by the sponsor, whichever came first, assessed up to approximately 2 years)
- DOR(From date of first dose until the date of first documented progression, death from any cause, loss of follow-up, withdrawal of informed consent, or study termination by the sponsor, whichever came first, assessed up to approximately 2 years)
- PFS(From date of first dose until the date of first documented progression, death from any cause, loss of follow-up, withdrawal of informed consent, or study termination by the sponsor, whichever came first, assessed up to approximately 2 years)
- OS(From date of first dose until the date of first documented progression, death from any cause, loss of follow-up, withdrawal of informed consent, or study termination by the sponsor, whichever came first, assessed up to approximately 2 years)
- Cmax(Up to approximately 1 year)
- Tmax(Up to approximately 1 year)
- t1/2(Up to approximately 1 year)
- AUC0-t(Up to approximately 1 year)
- AUC0-∞(Up to approximately 1 year)
- Cmin, ss(Up to approximately 1 year)
- Cmax, ss(Up to approximately 1 year)
- Tmax, ss(Up to approximately 1 year)
- t1/2, ss(Up to approximately 1 year)
- Cav, ss(Up to approximately 1 year)
- ADA and NAb(Up to approximately 1 year)